N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride, is a promising pharmaceutical agent, which is potent and selective Histamine H3 receptor ligand intended for the symptomatic treatment of cognitive disorders, dementia, attention deficit hyperactivity disorder, epilepsy, sleep disorders, sleep apnea, obesity, schizophrenia, eating disorders and pain. N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride and its synthesis is disclosed by Ramakrishna et al. in WO2012114348.
Currently N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride has completed preclinical studies and is ready to enter human clinical trials. The demand for N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride as a drug substance has increased substantially with the advent of its clinical testing. The future need for much larger amounts is projected due to the intended commercialization of N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride.
For the person skilled in art, it is a well known fact that various parameters will change during the manufacture of a compound on a large scale when compared to the synthetic procedures followed in laboratory. Therefore, there is a need to establish and optimize large scale manufacturing process. The process for the preparation of N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride disclosed in WO2012114348 was proved to be unsatisfactory for adaptation to the large scale manufacturing. Hence it is highly desirable to establish optimized manufacturing process of N-[4-(1-Cyclobutyl piperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride of formula (I), which is amenable to the large scale manufacturing of the compound.